Select therapeutic use:

Mood disorders:

Indications for: LATUDA

Major depressive episodes associated with bipolar I disorder as monotherapy in patients ≥10yrs and as adjunctive therapy with lithium or valproate in adults.

Clinical Trials:

Adults (Monotherapy)

  • Approval was based on a 6-week, multicenter, randomized, double-blind, placebo-controlled study of adult patients (mean age of 41.5 years, range 18 to 74) with major depressive episodes associated with bipolar I disorder, with or without rapid cycling, and without psychotic features (N=485).

  • Patients were randomized to receive one of two flexible-dose ranges of Latuda (20 to 60mg/day, or 80 to 120mg/day) or placebo.

  • The primary endpoint was the change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) score at Week 6. The key secondary endpoint was the Clinical Global Impression-Bipolar-Severity of Illness scale (CGI-BP-S).

  • At week 6, both doses of Latuda achieved superiority to placebo in reduction of MADRS and CGI-BP-S scores. Overall, the high dose range (80 to 120mg/day) did not provide additional benefit compared with the low dose range (20 to 60mg/day).

Adults (Adjunctive Therapy with Lithium or Valproate)

  • Approval was based on a  6-week, multicenter, randomized, double-blind, placebo-controlled study of adult patients (mean age of 41.7 years, range 18 to 72)  with major depressive episodes associated with bipolar I disorder, with or without rapid cycling, and without psychotic features (N=340). Patients who remained symptomatic after treatment with lithium or valproate were randomized to flexibly dosed Latuda 20 to 120 mg/day or placebo.  

  • The primary endpoint was the change from baseline in MADRS score at Week 6. The key secondary instrument was the CGI-BP-S scale. 

  • At week 6, Latuda was superior to placebo in reduction of MADRS and CGI-BP-S scores as an adjunctive therapy with lithium or valproate.

Pediatric Patients (10 to 17 years)  

  • Approval was based on a 6-week, multicenter, randomized, double-blind, placebo-controlled study of pediatric patients (10 to 17 years) with major depressive episode associated with bipolar I disorder, with or without rapid cycling, and without psychotic features (N=343). Patients were randomized to flexibly dosed LATUDA 20 to 80 mg/day or placebo.

  • The primary endpoint was the change from baseline in CDRS-R score at Week 6. The key secondary endpoint was the change from baseline in CGIBP-S depression score. 

  • At week 6, Latuda was superior to placebo in reduction of CDRS-R total score and CGI-BP-S depression score.

Adult Dosage:

Take with food (≥350 calories). Initially 20mg once daily. Usual range: 20–120mg/day; max 120mg/day. Moderate (CrCl 30 to <50mL/min) to severe renal impairment (CrCl <30mL/min), moderate hepatic impairment (Child Pugh Score 7–9): initially 20mg; max 80mg/day. Severe hepatic impairment (Child Pugh Score 10–15): initially 20mg; max 40mg/day. If moderate CYP3A4 inhibitors (eg, diltiazem, atazanavir, erythromycin, fluconazole, verapamil) is added concomitant to prescribed lurasidone therapy: reduce lurasidone dose to ½ of the original dose; if lurasidone is added concomitant to prescribed moderate CYP3A4 inhibitors: initially 20mg/day; max 80mg/day. Concomitant moderate CYP3A4 inducers (eg, bosentan, efavirenz, etravirine, modafinil, nafcillin): may need to increase lurasidone dose after chronic treatment (≥7 days) with inducer.

Children Dosage:

<10yrs: not established. Take with food (≥350 calories). 10–17yrs: initially 20mg once daily as monotherapy; may increase after 1 week based on response. Usual range: 20–80mg/day; max 80mg/day.

LATUDA Contraindications:

Concomitant strong CYP3A4 inhibitors (eg, ketoconazole, clarithromycin, ritonavir, voriconazole, mibefradil) and inducers (eg, rifampin, avasimibe, St. John's wort, phenytoin, carbamazepine).

Boxed Warning:

Increased mortality in elderly patients with dementia-related psychosis. Suicidal thoughts and behaviors.

LATUDA Warnings/Precautions:

Elderly with dementia-related psychosis (not approved use); increased risk of death or cerebrovascular events (eg, stroke, TIA). Increased risk of suicidal thoughts and behavior in children, adolescents, and young adults; monitor for clinical worsening or behavior changes in all patients. Discontinue if neuroleptic malignant syndrome occurs; consider discontinuing if tardive dyskinesia occurs. Cardio- or cerebrovascular disease. Hypovolemia. Dehydration. Diabetes risk factors; obtain baseline fasting blood sugar. Monitor for hyperglycemia, dyslipidemia, weight gain, hyperprolactinemia. Pre-existing low WBCs or history of leukopenia/neutropenia; monitor CBCs during 1st few months of therapy; discontinue if WBCs decline. Moderate to severe hepatic or renal impairment. History of seizures. Mania or hypomania (monitor). Dysphagia. Parkinson's disease. Dementia with Lewy Bodies. Exposure to extreme heat. Perform fall risk assessments when initiating and recurrently on long-term therapy. Write ℞ for smallest practical amount. Pregnancy. Nursing mothers.

LATUDA Classification:

Atypical antipsychotic.

LATUDA Interactions:

See Adults and Contraindications. Avoid grapefruit and grapefruit juice.

Adverse Reactions:

Somnolence, akathisia, extrapyramidal symptoms, nausea, rhinitis/rhinorrhea (80mg), vomiting, weight gain, insomnia; orthostatic hypotension and syncope possible.

Metabolism:

  • CYP3A4.

Drug Elimination:

  • Half-life: 18 hours.

  • Fecal (80%), renal (9%).

How Supplied:

Tabs—30, 90, 500

Psychosis:

Indications for: LATUDA

Schizophrenia.

Clinical Trials:

Adults

  • Approval was based on five 6-week, placebo-controlled studies in adults with schizophrenia. An active-control arm (olanzapine or quetiapine extended-release) was included in 2 studies to assess assay sensitivity.

  • The studies assessed psychiatric signs and symptoms at the end of week 6 by using the following:

    • Positive and Negative Syndrome Scale (PANSS), is a multi-item inventory of general psychopathology used to evaluate the effects of drug treatment in schizophrenia. PANSS total scores may range from 30 to 210. 

    • Brief Psychiatric Rating Scale derived (BPRSd), derived from the PANSS, is a multi-item inventory primarily focusing on positive symptoms of schizophrenia, whereas the PANSS includes a wider range of positive, negative and other symptoms of schizophrenia. The BPRSd consists of 18 items rated on a scale of 1 (not present) to 7 (severe). BPRSd scores may range from 18 to 126.

    • The Clinical Global Impression severity scale (CGI-S) is a clinician-rated scale that measures the subject’s current illness state on a 1- to 7-point scale.

  • At week 6, study results are as followed:

    • Study 1 - Latuda 40mg or 120mg/day achieved superiority to placebo on the BPRSd total score, and the CGI-S.

    • Study 2 - Latuda 80mg/day achieved superiority to placebo on the BPRSd total score, and the CGI-S.

    • Study 3 - Latuda 40mg or 120mg/day achieved superiority to placebo on the PANSS total score, and the CGI-S.

    • Study 4 - Latuda 80mg/day achieved superiority to placebo on the PANSS total score, and the CGI-S.

    • Study 5 - Latuda 80mg or 160mg/day achieved superiority to placebo on the PANSS total score, and the CGI-S.

Adolescents (13-17 years) 

  • Approval was based on a 6-week, multicenter, randomized, double-blind, placebo-controlled study of 326 adolescents (13 to 17 years) with schizophrenia. Patients were randomized to receive Latuda (40 or 80 mg/day) or placebo.  

  • The primary rating instrument used to assess psychiatric signs and symptoms was the PANSS. The key secondary instrument was the CGI-S.

  • At week 6, both doses of Latuda achieved superiority to placebo in reduction of PANSS and CGI-S scores. Overall, the 80mg/day dose did not provide additional benefit compared with the 40mg/day dose.

Adult Dosage:

Take with food (≥350 calories). Initially 40mg once daily. Usual range: 40–160mg/day; max 160mg/day. Moderate (CrCl 30 to <50mL/min) to severe renal impairment (CrCl <30mL/min), moderate hepatic impairment (Child Pugh Score 7–9): initially 20mg; max 80mg/day. Severe hepatic impairment (Child Pugh Score 10–15): initially 20mg; max 40mg/day. If moderate CYP3A4 inhibitors (eg, diltiazem, atazanavir, erythromycin, fluconazole, verapamil) is added concomitant to prescribed lurasidone therapy: reduce lurasidone dose to ½ of the original dose; if lurasidone is added concomitant to prescribed moderate CYP3A4 therapy: initially 20mg/day; max 80mg/day. Concomitant moderate CYP3A4 inducers (eg, bosentan, efavirenz, etravirine, modafinil, nafcillin): may need to increase lurasidone dose after chronic treatment (≥7 days) with inducer.

Children Dosage:

<13yrs: not established. Take with food (≥350 calories). 13–17yrs: initially 40mg once daily. Usual range: 40–80mg/day; max 80mg/day. Dose modifications: see Adult.

LATUDA Contraindications:

Concomitant strong CYP3A4 inhibitors (eg, ketoconazole, clarithromycin, ritonavir, voriconazole, mibefradil) and inducers (eg, rifampin, avasimibe, St. John's wort, phenytoin, carbamazepine).

Boxed Warning:

Increased mortality in elderly patients with dementia-related psychosis. Suicidal thoughts and behaviors.

LATUDA Warnings/Precautions:

Elderly with dementia-related psychosis (not approved use); increased risk of death or cerebrovascular events (eg, stroke, TIA). Increased risk of suicidal thoughts and behavior in children, adolescents, and young adults; monitor for clinical worsening or behavior changes in all patients. Discontinue if neuroleptic malignant syndrome occurs; consider discontinuing if tardive dyskinesia occurs. Cardio- or cerebrovascular disease. Hypovolemia. Dehydration. Diabetes risk factors; obtain baseline fasting blood sugar. Monitor for hyperglycemia, dyslipidemia, weight gain, hyperprolactinemia. Pre-existing low WBCs or history of leukopenia/neutropenia; monitor CBCs during 1st few months of therapy; discontinue if WBCs decline. Moderate to severe hepatic or renal impairment. History of seizures. Mania or hypomania (monitor). Dysphagia. Parkinson's disease. Dementia with Lewy Bodies. Exposure to extreme heat. Perform fall risk assessments when initiating and recurrently on long-term therapy. Write ℞ for smallest practical amount. Pregnancy. Nursing mothers.

LATUDA Classification:

Atypical antipsychotic.

LATUDA Interactions:

See Adults and Contraindications. Avoid grapefruit and grapefruit juice.

Adverse Reactions:

Somnolence, akathisia, extrapyramidal symptoms, nausea, rhinitis/rhinorrhea (80mg), vomiting, weight gain, insomnia; orthostatic hypotension and syncope possible.

Metabolism:

  • CYP3A4.

Drug Elimination:

  • Half-life: 18 hours.

  • Fecal (80%), renal (9%).

How Supplied:

Tabs—30, 90, 500